ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.2866-2del

dbSNP: rs1593681941
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001375 SCV001158573 pathogenic Wilson disease 2019-07-01 criteria provided, single submitter clinical testing The ATP7B c.2866-2delA variant (rs1377418826), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant abolishes the canonical splice acceptor site of intron 12, which is likely to disrupt gene function. Another variant at the same nucleotide (c.2866-2A>G) has been reported in individuals with Wilson disease and is considered disease-causing, suggesting this position is intolerant of variation (Aggarwal 2013, Huong 2018). Based on available information, the c.2866-2delA variant is considered to be pathogenic. References: Aggarwal A et al. Wilson disease mutation pattern with genotype-phenotype correlations from Western India: confirmation of p.C271* as a common Indian mutation and identification of 14 novel mutations. Ann Hum Genet. 2013 Jul;77(4):299-307. Huong NTM et al. Three novel mutations in the ATP7B gene of unrelated Vietnamese patients with Wilson disease. BMC Med Genet. 2018 Jun 18;19(1):104.
Genome-Nilou Lab RCV001001375 SCV001977296 pathogenic Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Invitae RCV001001375 SCV003018074 likely pathogenic Wilson disease 2022-07-11 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 811491). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 12 of the ATP7B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883).
Baylor Genetics RCV001001375 SCV004216462 likely pathogenic Wilson disease 2023-03-06 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.